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目的探讨Wilson病的临床病理学特征及其肝纤维化机制。方法对48例临床资料完整并行肝穿刺检查的Wilson病例做临床和实验室资料分析。采用光镜观察、电镜观察、Rhodanine/Rubeanicacid铜染色及网状纤维和胶原纤维染色探讨Wilson病的病理学特点;应用免疫组织化学方法观察肝组织内金属蛋白酶组织抑制因子TIMP1、TIMP2的表达,并以原位末端标记与αSMA免疫组织化学双标记法观测肝星状细胞(HSC)的活化与凋亡状况。结果本组患者发病年龄10.0±3.8岁,有家族史者29.2%,K F环阳性68.8%,血清铜蓝蛋白和铜氧化酶异常分别为93.0%和95.0%,血清ALT、AST、ALP、及GGT均值分别为正常上限值3.6、3.0、2.7和2.0倍。肝脏主要病变表现为汇管区及小叶内不同程度慢性炎症及界面炎,肝细胞小泡/微泡或大、小泡混合性脂肪变性,77.0%肝细胞内呈较弥漫性铜颗粒沉积,以腺泡I带肝细胞为甚,可见大而不整的凋亡小体、糖原核肝细胞、Mallory小体及嗜伊红颗粒肝细胞;超微观察示肝细胞内可见肿胀或怪异线粒体,溶酶体颗粒增多,并见泡状圆形包涵体。本组病例均存在不同程度肝纤维化,表现为早期汇管区扩大,中期纤维间隔形成及晚期肝硬化改变。活动性病变肝组织内,尤其在铜颗粒沉积明显区域活化HSC数目明显增加,凋亡减少,TIMP1、TIMP2表达量增强
Objective To investigate the clinicopathological features of Wilson’s disease and its mechanism of liver fibrosis. Methods Clinical data and laboratory data were analyzed in 48 Wilson cases with complete and concurrent liver biopsy. The pathological features of Wilson’s disease were investigated by light microscopy, electron microscopy, copper staining with Rhodanine / Rubeanicacid and reticular fibers and collagen fibers staining. The expressions of TIMP1 and TIMP2 were observed by immunohistochemistry The activation and apoptosis of hepatic stellate cells (HSC) were observed by both in situ end labeling and αSMA immunohistochemical double labeling. Results The age of onset was 10.0 ± 3.8 years old, family history was 29.2%, KF was 68.8%, serum ceruloplasmin and copper oxidase were 93.0% and 95.0%, serum ALT, AST, ALP and GGT The mean values were 3.6, 3.0, 2.7 and 2.0 times the upper limit of normal, respectively. The main pathological changes of the liver were chronic inflammation and interfacial inflammation with different degree in the portal area and the lobule, hepatocyte vesicles / microvesicles or mixed steatosis of small and small vesicles, diffuse copper particles deposition in 77.0% hepatocytes, I bubble soaked with hepatocytes is even larger, visible apoptotic bodies of large and small, glycogen nuclear hepatocytes, Mallory bodies and eosinophilic granulocytes; ultrastructural hepatocytes showed swollen or weird mitochondria, lysosomes Increased particles, and see bubble-shaped circular inclusions. This group of patients there are varying degrees of liver fibrosis, manifested as early portal area enlargement, the formation of interventricular septum and changes in advanced liver cirrhosis. Active lesions of liver tissue, especially in the obvious deposition of copper particles significantly increased the number of activated HSC, decreased apoptosis, TIMP1, TIMP2 expression increased